Several polysaccharides (carbohydrate polymers) of mannose (e.g., mannans), β(1,3) glucose (e.g., glucans), β(1,4) acetylated mannose (acemannans), β(1,4) N-acetyl-glucosamine (chitins), and heteropolysaccharides, such as rhamnogalacturonans (pectins), have been shown to stimulate the immune system.
Binding of polysaccharides to C-type lectin receptors induces immunostimulation, as shown by the increase in phagocytosis, proliferative responses, release of cytokines, and other activities of the immune system. Because of this immunostimulatory activity, these polysaccharides have been proposed for use in vaccine compositions. Of particular interest is mannan.
Mannan is a polymannose recognized by C-type lectin receptors, such as the mannose receptor (CD206) and DC-SIGN (CD209). Because of their presence on antigen-presenting cells, these receptors have been characterized for their uptake of mannose, fucose or glucose containing compounds. Binding of mannan to the mannose receptor for instance, induces endocytosis, followed by its delivery into the endosomal pathway. Early studies on mannnosylated antigens indicated that the presence of mannose residues on antigens greatly enhanced antigen-uptake and major histocompatibility complex (MHC) class II-restricted antigen presentation by dendritic cells (DCs). Conjugation of mannan to at least one antigen also enhances its uptake and presentation.
Although the immunostimulatory properties of certain polysaccharides have been known for some time, their use has been largely limited to research applications. This is due in part, to the strict regulations governing their use in a clinical setting, particularly with regard to humans. As a result, there is a need for further immunostimulatory and vaccine compositions for use in the treatment or prevention of diseases, as well as reliable methods for the preparation thereof.